Association of polymorphisms in the cyclin D1 and XPD genes and susceptibility to cancers of the upper aero-digestive tract.

DNA repair enzyme genetic polymorphisms have been postulated to increase the risk of certain cancers in the presence of tobacco carcinogen exposures. The XPD protein is an important component of the TFIIH transcription factor complex. XPD genetic polymorphisms resulting in amino acids substitutions may lead to alterations in TFIIH helicase activity, resulting in repair and transcription defects. Cyclin D1 is a key regulatory protein for the transition of cells from the G(1)-S cell cycle phase. The CCND1 G870A polymorphism has been reported to enhance alternate splicing of a stable mRNA variant, which may result in the bypass of the G(1)/S cell cycle checkpoint. In this study, XPD G23591A (Asp312Asn) and A35931C (Lys751Gln) polymorphisms and the CCND1 G870A splice variant frequencies were determined in 273 upper aero-digestive tract cancer cases and 269 controls. The XPD Asp312Asn variant frequency was significantly different among cases and controls and conferred an odds ratio (OR) of 1.3 (95% CI 1.0-1.8). However, individuals with the CCND1 G870A and XPD Lys751Gln variants had higher age adjusted ORs of 3.2 (95% CI 2.2-4.6) and 2.2 (95% CI 1.5-3.2), respectively. Furthermore, a significant gene-gene interaction was observed among cases with at least two variant alleles for both CCND1 and XPD genes [OR 7.09 (95% CI 4.03-12.5)]. Smokers with a combination of at least one variant allele of both CCND1 and XPD genes also had an elevated risk as compared to nonsmokers. This is the first study to suggest an associative interaction between XPD and CCND1 genetic polymorphisms, tobacco exposure, and cancer risk.

Buch S ，Zhu B ，Davis AG ，Odom D ，Siegfried JM ，Grandis JR ，Romkes M ... -  《MOLECULAR CARCINOGENESIS》

[Association of genetic polymorphisms in the DNA repair gene XPD with risk of lung and esophageal cancer in a Chinese population in Beijing].

Xing DY ，Qi J ，Tan W ，Miao XP ，Liang G ，Yu CY ，Lu WF ，Zhou CN ，Wu M ，Lin DX ... -  《-》

Specific combinations of DNA repair gene variants and increased risk for non-small cell lung cancer.

Popanda O ，Schattenberg T ，Phong CT ，Butkiewicz D ，Risch A ，Edler L ，Kayser K ，Dienemann H ，Schulz V ，Drings P ，Bartsch H ，Schmezer P ... -  《CARCINOGENESIS》

Polymorphisms in XPD exons 10 and 23 and bladder cancer risk.

Schabath MB ，Delclos GL ，Grossman HB ，Wang Y ，Lerner SP ，Chamberlain RM ，Spitz MR ，Wu X ... -  《CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION》

Association of the DNA repair gene XPD Asp312Asn polymorphism with p53 gene mutations in tobacco-related non-small cell lung cancer.

Gao WM ，Romkes M ，Day RD ，Siegfried JM ，Luketich JD ，Mady HH ，Melhem MF ，Keohavong P ... -  《CARCINOGENESIS》